Structural studies of aromatic amines and the dna intercalating compounds m-amsa and o-amsa: Comparison of mndo,am1, and pm3 to experimental and ab initio results

The ability of the MNDO, AM1, and PM3 semiempirical methods to reproduce pyramidalization at the nitrogen in 15 aromatic amines has been examined and compared to experimental and other theoretical results. AM1 consistently gives the best agreement. We have therefore reexamined the DNA intercalating compounds m-AMSA and o-AMSA using AM1.     

Evaluation of PM3, AM1, and MNDO for calculation of higher energy ionization potentials

Higher ionization energies were calculated with PM3, AM1, and MNDO for three series of molecules, representative small molecules, molecules containing heteroatoms, and sterically congested alkenes. Values from PM3, AM1, and MNDO were compared to experimental values. In most instances, the semiempirical calculations correctly predict the ordering of higher ionization energies. In the absence of steric hindrance, MNDO is the method of choice. Within groups of molecules, AM1 performs better on hydrocarbons, especially twisted hydrocarbons, than PM3. PM3 commonly gives sigma orbitals which are too high in energy compared to related pi orbitals. PM3 performed better than AM1 with molecules containing oxygen, but failed to give the correct geometry for hydrogen peroxide.     

Computational structural determination and energy landscape analysis of the hepatic carcinogen 2-(acetylamino)fluorene

 2-(Acetylamino)fluorene (AAF), a potent mutagen and a prototypical example of the mutagenic aromatic amines, forms covalent adducts to DNA after metabolic activation in the liver. A benchmark study of AAF is presented using a number of the most widely used molecular mechanics and semiempirical computational methods and models. The results are compared to higher-level quantum calculations and to experimentally obtained crystal structures. Hydrogen bonding between AAF molecules in the crystal phase complicates the direct comparison of gas-phase theoretical calculations with experiment, so Hartree–Fock (HF) and Becke–Perdew (BP) density functional theory (DFT) calculations are used as benchmarks for the semiempirical and molecular mechanics results. Systematic conformer searches and dihedral energy landscapes were carried out for AAF using the SYBYL and MMFF94 molecular mechanics force fields; the AM1, PM3 and MNDO semiempirical quantum mechanics methods; HF using the 3-21G*and 6-31G* basis sets; and DFT using the nonlocal BP functional and double numerical polarization basis sets. MMFF94, AM1, HF and DFT calculations all predict the same planar structures, whereas SYBYL, MNDO and PM3 all predict various nonplanar geometries. The AM1 energy landscape is in substantial agreement with HF and DFT predictions; MMFF94 is qualitatively similar to HF and DFT; and the MNDO, PM3 and SYBYL results are qualitatively different from the HF and DFT results and from each other. These results are attributed to deficiencies in MNDO, PM3 and SYBYL. The MNDO, PM3 and SYBYL models may be unreliable for compounds in which an amide group is immediately adjacent to an aromatic ring. Received: 26 May 2002 / Accepted: 12 December 2002 / Published online: 14 February 2003     

Semiempirical infrared spectra simulations for some aromatic amines of interest for azo dye chemistry.

A set of semiempirical methods (PM3, AM1, MNDO, MNDO3, INDO, CNDO and ZINDO/1) has been tested to find the best tool for the identification of aromatic amines by infrared spectroscopy. Analysed were 1,4-, 1,3-, 1,2-phenylenediamines and aniline, amines commonly used in the dye industry. Of all the semiempirical methods tested, AM1 showed the closest correspondence to experimental values. It provided the best linearity between the calculated and experimental frequencies (correlation coefficient, cc = 0.9993). In the range of -NH2 stretching vibrations, the best correspondence between the theoretical and experimental frequencies was achieved for the PM3 method (cc = 0.8369).     

Synthesis,X-ray Molecular Structure,and Semiempirical Calculations of a New Heteroarylpiperazine Derivative

The new piperazine derivative (1) was synthesized by linking a coumarin system to a heteroarylpiperazine via a propyloxy chain. Its molecular structure, as determined by X-ray diffractometry is compared to those computed by three semiempirical methods. PM3 and MNDO give the best accuracy in reproducing the bond distances and angles, respectively. AM1 gives the best agreement with X-ray in reproducing the whole three-dimensional (3D) structure of this molecule. An analysis of these results at the light of other similar previously reported is carried out.     

Testing electronic structure methods for describing intermolecular H...H interactions in supramolecular chemistry

In this article a wide variety of computational approaches (molecular mechanics force fields, semiempirical formalisms, and hybrid methods, namely ONIOM calculations) have been used to calculate the energy and geometry of the supramolecular system 2-(2'-hydroxyphenyl)-4-methyloxazole (HPMO) encapsulated in beta-cyclodextrin (beta-CD). The main objective of the present study has been to examine the performance of these computational methods when describing the short range H. H intermolecular interactions between guest (HPMO) and host (beta-CD) molecules. The analyzed molecular mechanics methods do not provide unphysical short H...H contacts, but it is obvious that their applicability to the study of supramolecular systems is rather limited. For the semiempirical methods, MNDO is found to generate more reliable geometries than AM1, PM3 and the two recently developed schemes PDDG/MNDO and PDDG/PM3. MNDO results only give one slightly short H...H distance, whereas the NDDO formalisms with modifications of the Core Repulsion Function (CRF) via Gaussians exhibit a large number of short to very short and unphysical H...H intermolecular distances. In contrast, the PM5 method, which is the successor to PM3, gives very promising results. Our ONIOM calculations indicate that the unphysical optimized geometries from PM3 are retained when this semiempirical method is used as the low level layer in a QM:QM formulation. On the other hand, ab initio methods involving good enough basis sets, at least for the high level layer in a hybrid ONIOM calculation, behave well, but they may be too expensive in practice for most supramolecular chemistry applications. Finally, the performance of the evaluated computational methods has also been tested by evaluating the energetic difference between the two most stable conformations of the host(beta-CD)-guest(HPMO) system.     

Tautomeric equilibria of heterocyclic molecules. A test of the semiempirical AM1 and MNDO-PM3 methods

Tautomeric equilibria (mainly of the lactam-lactim type) for a rather large number of six-membered heterocyclic molecules are calculated by the semiempirical AM1, MNDO-PM3, and MNDO methods. Except for compounds with adjacent pyridine-like lone pairs both AM1 as well as MNDO-PM3 give rather reliable predictions for relative stabilities of the various tautomeric species–comparable to quite high level ab initio calculations. The known errors associated with MNDO in the treatment of heterocyclic tautomerism are thus largely corrected in AM1 as well as MNDO-PM3. For 2-hydroxypyridine-pyrid-2(1H)-one the effect of self-association is less satisfactorily described by MNDO-PM3 than by AM1. MNDO-PM3 calculated relative stabilities of methylated derivatives are, however, in considerably closer agreement with experimental values than those obtained by AM1. Ionization potentials, especially those for lone-pair orbitals, are overestimated by all three semiempirical methods. MNDO-PM3 results for nitrogen lone-pair orbital energies are slightly better than those obtained by the AM1 or MNDO method.     

Theoretical calculations of the structure of a donor—acceptor stilbene, azobenzene and related molecules

The structures of a substituted stilbene, azobenzene, and two isomeric benzylidene anilines containing the 4-dimethyl-amino group at one end of the molecule and the 4′-nitro group at the other, have been calculated using the semiempirical MNDO, AM1, and PM3 methods and the ab initio HF/3-21G method. The results are compared with experimental data where available. The MNDO method gives a very poor account of the geometry of the stilbene, but both the AM1 and PM3 methods correctly predict the planarity of the substituted stilbene and nitrobenzylidene aniline but erroneously predict a non-planar structure for the azobenzene. In contrast, the ab initio method predicts planar structures for the substituted stilbene, azobenzene, and nitrobenzylidene aniline, and a twisted structure for the isomeric benzylidene nitroaniline, in line with crystallographic data. This loss of planarity for the benzylidene nitroaniline is almost certainly responsible for its smaller non-linear activity and for the hypsochromic shift observed in its low energy absorption band relative to the other molecules.     

Extension of the PDDG/PM3 and PDDG/MNDO semiempirical molecular orbital methods to the halogens

The new semiempirical methods, PDDG/PM3 and PDDG/MNDO, have been parameterized for halogens. For comparison, the original MNDO and PM3 were also reoptimized for the halogens using the same training set; these modified methods are referred to as MNDO' and PM3'. For 442 halogen-containing molecules, the smallest mean absolute error (MAE) in heats of formation is obtained with PDDG/PM3 (5.6 kcal/mol), followed by PM3' (6.1 kcal/mol), PDDG/MNDO (6.6 kcal/mol), PM3 (8.1 kcal/mol), MNDO' (8.5 kcal/mol), AM1 (11.1 kcal/mol), and MNDO (14.0 kcal/mol). For normal-valent halogen-containing molecules, the PDDG methods also provide improved heats of formation over MNDO/d. Hypervalent compounds were not included in the training set and improvements over the standard NDDO methods with sp basis sets were not obtained. For small haloalkanes, the PDDG methods yield more accurate heats of formation than are obtained from density functional theory (DFT) with the B3LYP and B3PW91 functionals using large basis sets. PDDG/PM3 and PM3' also give improved binding energies over the standard NDDO methods for complexes involving halide anions, and they are competitive with B3LYP/6-311++G(d,p) results including thermal corrections. Among the semiempirical methods studied, PDDG/PM3 also generates the best agreement with high-level ab initio G2 and CCSD(T) intrinsic activation energies for S(N)2 reactions involving methyl halides and halide anions. Finally, the MAEs in ionization potentials, dipole moments, and molecular geometries show that the parameter sets for the PDDG and reoptimized NDDO methods reduce the MAEs in heats of formation without compromising the other important QM observables.     

Enthalpy of formation of adamantane alkyl derivatives

The enthalpies of formation of adamantane alkyl derivatives were calculated by the semiempirical quantum chemical methods PM3, MINDO, AM1 and MNDO of the MOPAC software package. Comparison of the calculated values with the experimental data showed that the best correlation gave the PM3 method. Using this method and linear regression equation derived by us we calculated enthalpies of formation of twenty-two alkyl derivatives of adamantane.     

Calculations of the enthalpies of formation of oxygen-containing adamantane derivatives by quantum-chemical methods

The enthalpies of formation of oxygen-containing adamantane derivatives were calculated using the semiempirical quantum-chemical PM3, MINDO, AM1, and MNDO methods implemented in the MOPAC package. The calculated and experimental values were compared. The best correlation was obtained for AM1 calculations. This method was therefore used to calculate the enthalpies of formation of 20 oxygen-containing adamantane derivatives.     

Comparative semiempirical and ab initio study of the harmonic vibrational frequencies of aniline—I. The ground state

The harmonic vibrational frequencies of the ground state S₀ of aniline obtained from various ab initio methods [6-31G, 6-31G(*) and 6-31G* basis sets] and semiempirical methods (MINDO/3, MNDO, AM1 and PM3) have been compared to the experimental vibrational spectra. Detailed theoretical analyses of the atomic Cartesian displacements of all normal modes are presented. The semiempirical PM3 method reproduces the experimental frequencies of aniline with comparable accuracy to the ab initio methods. Ale PM3 method will be useful in predicting the vibrational spectra of larger aromatic amines.     

Conformational behavior of some hydroxamic acids

The conformational preferences of a few hydroxamic acids are investigated by the density functional B3LYP/6-311++G**//B3LYP16-31G* and semiempirical AM1 and PM3 methods in this work. It is found that both semiempirical methods give satisfactory results in comparison with sophisticated DFT and ab initio calculations, except for the activation barriers, which are overestimated. Of the two semiempirical methods, while the PM3 method gives better results for relative stabilities, AM1 geometries are in slightly better agreement with the experiments. The keto forms are found to be most stable and the reaction pathways for the interconversion between the keto and enol forms have been deduced. The effect of solvation on the reaction has also been investigated, as has the effect of methyl substitution at the carbon and nitrogen atoms. All the investigated acids exhibit N-acid behavior.     

Comparative study between ab initio and semiempirical electrostatic potentials on molecular surfaces

The electrostatic potentials of 21 molecules containing different functional groups has been computed at the ab initio RHF/6-31G* level on a series of solvent accessible surfaces and compared with MNDO, AM1, and PM3-derived pontentials. We analyzed in detail the distribution of electrostatic potentials on the surfaces around their maximum and minimum values and found out that consistently MNDO gives results similar to ab initio potentials. The actual values of the MNDO electrostatic potentials show a systematic deviation from the “correct” results, but the pattern of the MEP distribution on the surface is similar to that of the ab initio results. In contrast, PM3 fails in some cases to give even the correct number or distribution of “hot spots” of potential (low MEP) on the surface. AM1 behaves somewhere between these two semiempirical methods. As a conclusion, MNDO would be suggested as the best approach to analyses requiring a fast and efficient mapping of electrostatic potentials on simplified models of molecular surfaces. © 1993 John Wiley & Sons, Inc.     

Structures and energies of D-galactose and galabiose conformers as calculated by ab initio and semiempirical methods

Optimized geometries and total energies of some conformers of alpha- and beta-D-galactose have been calculated using the RHF/6-31G* ab initio method. Vibrational frequencies were computed at the 6-31G* level for the conformers that favor internal hydrogen bonding, in order to evaluate their enthalpies, entropies, Gibbs free energies, and then their structural stabilities. The semiempirical AM1, PM3, MNDO methods have also been performed on the conformers GG, GT, and TG of alpha- and beta-D-galactose. In order to test the reliability of each semiempirical method, the obtained structures and energies from the AM1, PM3, and MNDO methods have been compared to those achieved using the RHF/6-31G* ab initio method. The MNDO method has not been investigated further, because of the large deviation in the structural parameters compared with those obtained by the ab initio method for the galactose. The semiempirical method that has yielded the best results is AM1, and it has been chosen to perform structural and energy calculations on the galabiose molecule (the disaccharides constituted by two galactose units alpha 1,4 linked). The goal of such calculations is to draw the energy surface maps for this disaccharide. To realize each map, 144 different possible conformations resulting from the rotations of the two torsional angles psi and phi of the glycosidic linkage are considered. In each calculation, at each increment of psi and phi, using a step of 30 degrees from 0 to 330 degrees, the energy optimization is employed. In this article, we report also calculations concerning the galabiose molecule using different ab initio levels such as RHF/6-31G*, RHF/6-31G**, and B3Lyp/6-31G*.     

Comparison of semiempirical calculations for silicon compounds

A comparison is made of the performance of the MINDO/3, MNDO, AM1, and PM3 methods in calculating the nature of the dimer reconstruction observed on the silicon (100) crystal surface. Based on this case study we conclude that MINDO/3 gives the most realistic results, with PM3 calculations being quite similar but both MNDO and AM1 missing some key features of this system and giving rather unrealistic charge distributions. Hence use of PM3 is recommended for Si containing molecules where a lack of parameters or other restrictions prevent the use of MINDO/3.     

A comparison of semiempirical and ab initio transition states for HF elimination in unimolecular decompositions

The transition states for unimolecular HF elimination from a series of methylene halides and vinyl halides have been located and properly characterized at the AM 1, MNDO , PM 3, RHF /6-311G (d, p), and MP 2/6-311G (d, p) levels. Whereas the semiempirical MO methods deal well with the structures of the stable molecules, the structural differences between the ab initio and semiempirical transition states are considerably larger. The AM 1 and PM 3 activation energies appear to be relatively more accurate. © 1994 John Wiley & Sons, Inc.     

Accurate parametrized variational calculations of the molecular electronic polarizability by NDDO‐based methods

The variational method for the calculation of the electronic polarizability of molecules within the NDDO‐based semiempirical MO methods MNDO, AM1, and PM3 was parametrized to improve its accuracy. A training set of 156 compounds was used to fit 34 parameters simultaneously for 12 elements using a simplex optimization. The resulting parameters were tested for a test set of 83 molecules and the calculated polarizabilities compared with the experimental data. For AM1, the RMS deviation between experimental and calculated polarizabilities was reduced from 2.99 (using the original variational treatment) to 0.70 ų for the test set and from 2.81 to 0.40 ų for the training set. MNDO and PM3 gave similar improvements. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 75: 17–31, 1999     

Enthalpy of formation of thiophene derivatives

The enthalpy of formation in the gas phase has been calculated for 21 carbonyl compounds of the thiophene series with the aid of the PM3, MINDO, AM1, and MNDO semiempirical quantum-chemical methods. Comparison of them with experimental data showed that the best linear correlation was achieved with the PM3 method. The latter in conjunction with a developed linear regression equation has been used to predict the enthalpy of formation of 22 carboxylic acids and ketones of the thiophene series.     

Correlation of singlet-triplet gaps for aryl carbenes calculated by MINDO/3, MNDO,AM1, and PM3 with Hammett-type substituent constants

Heats of formation, atomic charges, and geometries of some 110 structures involving substituted singlet and triplet phenyl and 4,4-dimethyl-1,4-dihydronaphthalene carbenes and the corresponding diazomethanes were calculated by MINDO/3, MNDO, AM1, and PM3 semiempirical molecular orbital methods. The singlet-triplet gaps for AM1 and PM3 calculations for the para derivatives in both systems have been successfully correlated with Brown σ⁺ constants. Good correlations with σ⁺ were found for the charges on the carbenic centers of the singlets as well as with the energy barrier for rotation of the aryl group about the C-C single bond in substituted singlet phenylcarbenes. Comparisons of these results with experimental data indicate that AM1 and PM3 are much better than MNDO and MINDO/3 in predicting the intrinsic substituent effects in singlet carbenes.